Conceptually new sulfone analogues of the hormone 1α,25- dihydroxyvitamin D3

Synthesis and preliminary biological evaluation

Gary H. Posner, Qiang Wang, Gyoonhee Han, Jae Kyoo Lee, Kenneth Crawford, Sarvenaz Zand, Henry Brem, Sara Peleg, Patrick Dolan, Thomas W. Kensler

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

A conceptually new series of vitamin D3-like nonfluorinated and fluorinated 16-ene side chain tert-butyl sulfones 3-7 has been synthesized. Even though these novel C,D-ring side chain analogues of the hormone 1α,25- dihydroxyvitamin D3 (1, 1,25D3) lack a terminal OH group, thought previously to be essential for high biological activity, they are highly antiproliferative and, in several cases, transcriptionally active in vitro but desirably noncalcemic in vivo. The side chain sulfone group may be binding to the nVDR as a hydrogen-bond acceptor, in contrast to the hydrogen- bond donor function of the 25-OH group of natural 1,25D3.

Original languageEnglish
Pages (from-to)3425-3435
Number of pages11
JournalJournal of Medicinal Chemistry
Volume42
Issue number18
DOIs
Publication statusPublished - 1999 Sep 9

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Sulfones
Calcitriol
Hydrogen
Hormones
Cholecalciferol
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Posner, Gary H. ; Wang, Qiang ; Han, Gyoonhee ; Lee, Jae Kyoo ; Crawford, Kenneth ; Zand, Sarvenaz ; Brem, Henry ; Peleg, Sara ; Dolan, Patrick ; Kensler, Thomas W. / Conceptually new sulfone analogues of the hormone 1α,25- dihydroxyvitamin D3 : Synthesis and preliminary biological evaluation. In: Journal of Medicinal Chemistry. 1999 ; Vol. 42, No. 18. pp. 3425-3435.
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abstract = "A conceptually new series of vitamin D3-like nonfluorinated and fluorinated 16-ene side chain tert-butyl sulfones 3-7 has been synthesized. Even though these novel C,D-ring side chain analogues of the hormone 1α,25- dihydroxyvitamin D3 (1, 1,25D3) lack a terminal OH group, thought previously to be essential for high biological activity, they are highly antiproliferative and, in several cases, transcriptionally active in vitro but desirably noncalcemic in vivo. The side chain sulfone group may be binding to the nVDR as a hydrogen-bond acceptor, in contrast to the hydrogen- bond donor function of the 25-OH group of natural 1,25D3.",
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Posner, GH, Wang, Q, Han, G, Lee, JK, Crawford, K, Zand, S, Brem, H, Peleg, S, Dolan, P & Kensler, TW 1999, 'Conceptually new sulfone analogues of the hormone 1α,25- dihydroxyvitamin D3: Synthesis and preliminary biological evaluation', Journal of Medicinal Chemistry, vol. 42, no. 18, pp. 3425-3435. https://doi.org/10.1021/jm990267c

Conceptually new sulfone analogues of the hormone 1α,25- dihydroxyvitamin D3 : Synthesis and preliminary biological evaluation. / Posner, Gary H.; Wang, Qiang; Han, Gyoonhee; Lee, Jae Kyoo; Crawford, Kenneth; Zand, Sarvenaz; Brem, Henry; Peleg, Sara; Dolan, Patrick; Kensler, Thomas W.

In: Journal of Medicinal Chemistry, Vol. 42, No. 18, 09.09.1999, p. 3425-3435.

Research output: Contribution to journalArticle

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AU - Posner, Gary H.

AU - Wang, Qiang

AU - Han, Gyoonhee

AU - Lee, Jae Kyoo

AU - Crawford, Kenneth

AU - Zand, Sarvenaz

AU - Brem, Henry

AU - Peleg, Sara

AU - Dolan, Patrick

AU - Kensler, Thomas W.

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